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Biomedical subjects

T A Merritt

Publications and source records attributed to T A Merritt.

At least 91 records · Page 5Linked to original sources
PubMed1986

Prophylactic treatment of very premature infants with human surfactant.

We undertook a randomized, controlled trial to determine whether human surfactant administered endotracheally at birth to very premature infants (gestational age, 24 to 29 weeks) would prevent the respiratory distress syndrome or reduce its severity. Thirty-one treated infants (birth weight, 938 +/- 286 g) were compared in a blinded fashion with 29 control infants (birth weight, 964 +/- 174 g). The lecithin/sphingomyelin ratio was less than 2 in all infants, and phosphatidylglycerol was not present in amniotic fluid or tracheal fluids at birth, indicating a deficiency of surfactant in the lungs. The principal dependent variables were neonatal death, the incidence of bronchopulmonary dysplasia, and the infant's requirement for respiratory support (and its complications). The surfactant-treated group had significantly fewer deaths than the control group (16 percent vs. 52 percent, P less than 0.001), fewer cases of bronchopulmonary dysplasia (16 percent vs. 31 percent), and significantly fewer cases of pulmonary interstitial emphysema (P less than 0.001) and pneumothorax (P less than 0.02). Prophylactic treatment with human surfactant also substantially reduced the period of neonatal intensive care. We conclude that treatment with human surfactant offers promise for improving the survival of very premature infants with a surfactant deficiency and for reducing the pulmonary sequelae of the respiratory distress syndrome.

Amniotic Fluid↗
PubMed1986

Therapeutic effects of a ketogenic diet in Rett syndrome.

Seven girls (age 5 to 10 years) with Rett syndrome were investigated extensively. In 6 patients elevations of blood pyruvate were found. Blood lactate levels were marginally elevated. Two patients had variably elevated blood glucose levels. Metabolic studies were otherwise normal apart from minimally elevated blood ammonia levels in 3 of 5 patients tested, 2 of whom were on valproic acid. All 7 patients had anticonvulsant resistant seizures. EEG changes included generalized slowing and multifocal spike wave discharges, and pseudo-periodic burst-suppression patterns during sleep. Respiratory monitoring revealed apneic episodes only during the waking record. Six patients were below the 5th centile for weight despite normal caloric intake. Treatment with ketogenic diets, using medium chain triglyceride (MCT) oil when possible, has improved seizure control in the 5 patients who could tolerate the diet. Slight behavioral and motor improvement has occurred in these 5 patients and 6 of 7 patients on high fat diets have gained weight. With a possible defect in carbohydrate metabolism and a difficult seizure disorder, use of a ketogenic diet is logical and appears to produce clinical benefit in patients with Rett Syndrome.

Ammonia↗
PubMed1986

Human surfactant treatment of severe respiratory distress syndrome: pulmonary effluent indicators of lung inflammation.

Pulmonary effluent from infants who received exogenous human surfactant for severe respiratory distress syndrome was evaluated for inflammatory changes previously identified with lung injury during the first 2 weeks after birth. The number of pulmonary effluent inflammatory cells was higher only on day 1 in infants given surfactant. No other evidence of enhanced inflammation was detected in cytologic assessment of tracheal secretions. The classical pathway of complement was not activated in infants given surfactant or in control infants 2 weeks after birth. Albumin content of airway secretions was higher on the first day but not significantly altered on subsequent days. Human surfactant treatment was not associated with increased proteolytic activity, measured as neutrophilic elastase per milligram of albumin in lung effluent, but was associated with significantly higher alpha 1-proteinase inhibitor levels than in control infants from days 2 to 7 after birth. These findings provide evidence that exogenous human surfactant instilled into the lungs of preterm infants with severe respiratory distress syndrome is not associated with enhanced lung inflammation, compared with conventional mechanical ventilation alone. These data support additional clinical trials using human surfactant.

Albumins↗
PubMed1986

Reconstitution of surfactant activity using purified human apoprotein and phospholipids measured in vitro and in vivo.

The major apoprotein of human lung surfactant was isolated from amniotic fluid obtained at term gestation. It was found to be a disulfide-linked oligomer composed of polypeptide chains of 35,000 daltons. The monomeric unit was shown to be a glycoprotein, and treatment with peptide: N-glycosidase F resulted in a decrease in molecular weight to 31,000 daltons. The isolated apoprotein could be recombined in the presence of Ca++ with the phospholipids dipalmitoylphosphatidylcholine and phosphatidylglycerol (3:1) at a weight ratio of 1:100. The surface tension (gamma min) measured on a pulsating bubble formed in 4 mg/ml of phospholipids was reduced from 32.3 +/- 2.0 dyn X cm-1 to 18.0 +/- 0.6 dyn X cm-1 after 15 s when 1% apoprotein was present. Reduction of disulfide bonds and deglycosylation of the apoprotein did not alter its ability to lower gamma min. Fetal rabbits of 27 days gestation had instilled intratracheally at delivery, saline, phospholipids, phospholipids plus apoprotein, or natural human surfactant. The latter 2 resulted in increased lung compliance and striking improvement in homogeneous alveolar expansion when the lungs were expanded to 10 cm H2O pressure, fixed, and viewed histologically. This effect was also shown to be independent of the disulfide-dependent oligomeric structure of the apoprotein or its state of glycosylation. The surfactant produced by recombination of the phospholipids with the isolated apoprotein was, therefore, shown to be biophysically active both in vitro and in vivo. These data suggest that apoprotein can be recombined with phospholipids to produce a biologically active surfactant for use in clinical trials of human surfactant replacement.

Animals↗
PubMed1986

Effects of prostaglandins on the pulmonary vascular bed of newborn rats with chronic hypoxia.

We investigated the effects of prostaglandins (PG) E1, I2 and D2 on the pulmonary vascular bed of newborn rats subjected to chronic hypoxia. Forty seven newborn rats were exposed to chronic hypoxia (10% oxygen) for 23 days and divided into five groups which received PGE1 (N = 10), PGI2 (N = 9), PGD2 (N = 11), placebo (N = 9) or served as controls (N = 8). The PG's were administered by implanting slow release subcutaneous pellets delivering an average daily dose of 1 microgram. Thirteen newborn rats in room air received either placebo or served as controls. All rats were killed after 23 days and heart-lung preparations were perfusion fixed with glutaraldehyde. Appropriate blocks were processed for quantitative morphometry of the pulmonary parenchyma, arteries and arterioles. For analysis the pulmonary vessels were grouped by external diameter, i.e. 30-50 mu and 50-100 mu. External diameter/lumen diameter, an index of medial smooth muscle mass, was 1.39 +/- 0.02 in room air controls, this index of medial muscle mass was significantly increased (p less than 0.01) to 1.53 +/- 0.03 in hypoxic controls and the PGD2 and PGI2 groups. However, the PGE1 group did not have medial hypertrophy evidenced by a medial muscle mass index of 1.34 +/- 0.04, similar to room air controls. These findings suggest that PGE1 may prevent the development of medial hypertrophy that occurs in chronic hypoxia.

Alprostadil↗
PubMed1986

Effect of surfactant substitution on lung effluent phospholipids in respiratory distress syndrome: evaluation of surfactant phospholipid turnover, pool size, and the relationship to severity of respiratory failure.

The turnover and pool size of surfactant has been studied in animals, but there is little similar information in humans. In the present investigation lung effluent phospholipids were studied in 29 small preterm infants with severe RDS. Thirteen were treated with mechanical ventilation, and 16 additionally received natural human surfactant. The first dose (60 mg surfactant/kg body wt) was given between 2 and 10 h of age, and the surfactant was given again if there was an insufficient response. Together 260 aspirates, recovered during routine suctioning of the airways, were analyzed for phospholipids. Phosphatidylglycerol, present only in exogenous surfactant, was used as a specific marker to estimate the apparent pool size and the half-life of surfactant phospholipid. In addition, the saturated phosphatidylcholine/sphingomyelin ratios were correlated with the ventilatory index (mean airway pressure X fractional inspiratory oxygen/arterial oxygen tension). There was a linear correlation between the ventilatory index and the saturated phosphatidylcholine/sphingomyelin (r approximately -0.70) but no consistent correlation between the ventilatory index and the amount of phospholipids in the aspirate. The saturated phosphatidylcholine/sphingomyelin ratio increased during the surfactant-induced remission of respiratory failure, decreased during the recovery. The control infants tended to have lower saturated phosphatidylcholine/sphingomyelin ratios during the first week than the surfactant-treated infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Half-Life↗
PubMed1986

Ventriculoperitoneal shunts in low birth weight infants with intracranial hemorrhage: neurodevelopmental outcome.

Fifty preterm infants (mean birth weight, 1266 +/- 303 g; mean gestational age, 30 +/- 2 weeks) who required a ventriculoperitoneal (VP) shunt for posthemorrhagic hydrocephalus (92% with Grade III or IV hemorrhage) were followed for neurodevelopmental problems. VP shunts were placed at a median age of 29 days (range, 18 to 87 days) after serial lumbar punctures failed to control progressive and symptomatic ventriculomegaly. A total of 34 infants (68%) required one shunt revision or more, and the overall infection rate per patient was 50%. Seven infants died, 2 from shunt infections. The infants were evaluated with audiological, ophthalmological, and neurodevelopmental examinations. Of the survivors, 11 (28%) have severe visual loss and 10 (24%) have hearing impairment. Of the infants, 21 (49%) have severe motor handicaps and 19 (38%) have seizure disorders. Developmental and motor scores were obtained using the Bayley or Knobloch-Gesell scales. Seven infants (18%) have normal developmental outcomes; 26 (60%) have multiple handicaps. Grade IV hemorrhage or the occurrence of seizures was a predictor of poor neurodevelopmental outcome. We conclude that progressive posthemorrhagic hydrocephalus in low birth weight infants is associated with multiple handicaps despite early VP shunt placement.

Cerebral Hemorrhage↗
PubMed1986

Surfactant-anti-surfactant immune complexes in infants with respiratory distress syndrome.

The authors sought to determine whether treatment of respiratory distress syndrome (RDS) with human surfactant resulted in the formation of detectable circulating immune complexes. Preterm infants with severe RDS were divided into two groups: one group received human surfactant by intratracheal instillation and the other group did not. Both groups received ventilatory management involving intermittent mandatory ventilation. Plasma samples were drawn from these babies prior to treatment and at intervals thereafter. The authors developed an ELISA assay specific for surfactant-anti-surfactant immune complexes and analyzed the plasma samples for such immune complexes. Complement levels were also measured. They found that with time plasma from RDS infants in both groups showed evidence of surfactant-anti-surfactant immune complex formation. The concentrations of immune complexes generally peaked within the first week of life and then appeared to diminish over 1-4 weeks after birth in RDS infants. There was no evidence at any time in either group of immune-complex-mediated injury or of decreased serum complement levels. It is concluded that circulating immune complexes between surfactant and antibodies to surfactant are probably found in most neonates with respiratory distress syndrome, that they do not produce pulmonary damage detectable by clinical and serologic means, and that treatment of neonatal RDS with human surfactant similarly does not produce lung injury as determined with these techniques.

Antibody Specificity↗
PubMed1985

Exogenous human surfactant for treatment of severe respiratory distress syndrome: a randomized prospective clinical trial.

We performed a randomized, prospective clinical trial comparing intratracheal administration of human surfactant with conventional treatment with intermittent mandatory mechanical ventilation alone for treatment of severe respiratory distress syndrome in preterm infants of less than 30 weeks gestation. Twenty-two infants (mean gestational age 27.0 weeks, mean birth weight 987 gm) were given surfactant, and 23 infants (mean gestational age 27.2 week, mean birth weight 1055 gm) received intermittent mandatory ventilation. Infants given surfactant required less FiO2 during the first week, had lower mean airway pressure during the first 48 hours, and had improved ventilatory index and a/A PO2 ratio. Death or the occurrence of bronchopulmonary dysplasia was significantly less among infants given surfactant (P = 0.019). Pneumothorax, pulmonary interstitial emphysema, and need for FiO2 greater than or equal to 0.3 for greater than 30 days was significantly less in the surfactant group. This trial confirms the efficacy of treatment with human surfactant in preterm infants with severe respiratory distress syndrome.

Amniotic Fluid↗
PubMed1985

Respiratory distress syndrome treated with human surfactant: radiographic findings.

Chest radiographs of 18 newborns treated with endotracheal instillation of human surfactant for respiratory distress syndrome (RDS) were compared with those of 18 similar but untreated infants. In the treated infants, severity of RDS significantly improved after surfactant administration. Most treated infants (16/18) exhibited a left-to-right shunt, presumably through a patent ductus arteriosus; similar findings were noted in untreated infants (17/18). Complications of respiratory assistance in the treated infants included transient pulmonary interstitial emphysema (n = 1), pneumothorax (n = 1), and mild (n = 4) to moderate (n = 2) bronchopulmonary dysplasia; the incidences of these complications did not exceed those in untreated infants. In three treated infants, a transient interstitial lung disease developed 3-4 days after surfactant administration.

Ductus Arteriosus, Patent↗
PubMed1984

Prolonged bleeding time in preterm infants receiving indomethacin for patent ductus arteriosus.

Sequential bleeding times were performed on 25 preterm infants receiving intravenous indomethacin for closure of the patent ductus arteriosus. Prolongation of bleeding time was observed after the initial dose of indomethacin, with an increase from a pretreatment mean of 3.6 minutes to 8.7 minutes. The bleeding time was not further prolonged at the end of the three-dose course of indomethacin, but was still elevated 48 hours after the completion of therapy. Clinical bleeding developed in six of the patients, but was generally limited to occult hematuria. Serial echoencephalography during indomethacin therapy showed progression from mild periventricular-intraventricular hemorrhage to moderate or severe grades in five of 21 infants at risk for this complication. However, no clear temporal relationship between indomethacin administration and intraventricular hemorrhage extension was observed, and no difference in the degree of bleeding time prolongation was noted between infants with and without hemorrhage extension. Other factors, including surfactant deficiency, amount of volume expansion used, and lowest PO2 in the first day of life, did distinguish those with hemorrhage extension. The results suggest that indomethacin-induced platelet dysfunction is not associated with major hemorrhagic complications in the majority of preterm infants with patent ductus arteriosus.

Bleeding Time↗
PubMed1983

Elastase and alpha 1-proteinase inhibitor activity in tracheal aspirates during respiratory distress syndrome. Role of inflammation in the pathogenesis of bronchopulmonary dysplasia.

Pulmonary effluent samples were obtained from 26 preterm or term infants throughout the period of endotracheal intubation. Infants with respiratory distress syndrome, infants with this disorder developing bronchopulmonary dysplasia, and intubated infants without lung disease were compared daily in terms of lung effluent cellularity, albumin, elastase activity, alpha 1-proteinase content and activity, and elastase inhibitory capacity. The elastase activity was determined to be neutrophilic in origin. Polyacrylamide gel electrophoresis of pulmonary effluents from two infants with respiratory distress syndrome and exposed to FiO2 greater than or equal to 0.6 up to 6 d revealed cleavage of alpha 1-proteinase inhibitor to a 47,000-mol weight fragment suggestive of oxidation. Pulmonary effluent neutrophils, macrophages, and elastase activity were increased by day 3 of life in infants with respiratory distress syndrome eventually developing bronchopulmonary dysplasia. Elastase inhibitory capacity and alpha 1-proteinase inhibitor activity were reduced in infants developing chronic lung disease. Bronchopulmonary dysplasia developed in infants with enhanced inflammatory response, but with less or inhibited antiprotease activity.

Albumins↗